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Combined-modality treatment effective for muscle-invasive bladder cancer

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November 25, 2014

Patients with muscle-invasive bladder cancer who underwent bladder-preserving combined-modality therapy experienced disease-specific survival comparable to that typically observed with cystectomy, according to results of a pooled analysis.

Radical cystectomy remains standard treatment for muscle-invasive bladder cancer, yet bladder-preserving treatment strategies have improved due to evolution of radiation therapy, chemotherapy and patient selection, according to background information provided in the study.

Raymond H. Mak, MD, of the department of radiation oncology at Brigham and Women’s Hospital/Dana-Farber Cancer Institute, and colleagues reviewed data on 468 patients with muscle-invasive bladder cancer enrolled in six multicenter, prospective Radiation Therapy Oncology Group (RTOG) bladder-preservation trials.

These trials evaluated use of combined-modality therapy with maximal transurethral resection of bladder tumor (TURBT), radiotherapy and concurrent chemotherapy. Cystectomy was reserved for salvage treatment.

Median age of patients was 66 years (range, 34-93). The majority of patients (61%) had stage T2 tumors, whereas 35% had T3 tumors and 4% had T4a tumors.

Key endpoints included OS, disease-specific survival, muscle-invasive and non-muscle invasive local failure, and distant metastases.

Across studies, 69% of patients achieved complete response to combined-modality therapy.

Median follow-up was 4.3 years for the entire study population and 7.8 years among the 205 patients alive at the time of the analysis.

Mak and colleagues reported 5-year OS of 57% and 10-year OS of 36%. Rates of disease-specific survival were 71% at 5 years and 65% at 10 years.

The rate of muscle-invasive local failure was 13% at 5 years and 14% at 10 years, whereas the rate of non–muscle-invasive local failure was 31% at 5 years and 36% at 10 years. Incidence of distant metastases was 31% at 5 years and 35% at 10 years.

“Given the low incidence of late recurrences with long-term follow-up, combined-modality therapy can be considered as an alternative to radical cystectomy, especially in elderly patients not well-suited for surgery,” Mak and colleagues concluded.

The findings demonstrate that — when counseling patients with muscle-invasive bladder cancer about their treatment options — organ-sparing tri-modality therapy cannot be ignored, Claus Rodel, MD and Christian Weiss, MD, both of Goethe-University Frankfurt am Main in Germany, wrote in an accompanying editorial.

“As more experience is acquired with organ-sparing treatment in bladder cancer, it is clear that future clinical and basic research will focus on two main topics: first, the proper selection of patients who will most likely benefit from the respective treatment alternatives, and second, the optimization of the respective treatment components, including optimization of radiation techniques and fractionation schedules as well as incorporation of novel cytotoxic and biologic agents,” Rodel and Weiss wrote. “Inclusion of molecular markers that predict response and innovative imaging techniques, such as diffusion-weighted magnetic resonance imaging, to monitor response to tri-modality therapy may also help to improve patient selection and management.”

For more information:

  • Mak RH. J Clin Oncol. 2014; doi:10.1200/JCO.2014.57.5548.
  • Rodel C and Weiss C. J Clin Oncol. 2014; doi:10.1200/JCO.2014.58.5521

Disclosure: The researchers report consultant or advisory roles with Bayer, Celgene and Medivation/Astellas; stock or other ownership in Boehringer Ingelheim, Pfizer and Puma; and research funding, employment relationships, and travel or other expenses from Puma.

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PERSPECTIVE
Stephen B. Riggs

Stephen B. Riggs

The article by Mak and colleagues adds to the growing support of bladder preservation with maximal transurethral resection of the bladder tumor (TURBT) in combination with radiation and chemotherapy (tri-modal therapy) in patients with muscle-invasive disease. The long-term outcomes they present will serve as an updated benchmark, as well as enhance the information available to convey to our patients and colleagues. Their results underscore a bias to choose patients wisely and to follow closely in order to provide an opportunity for salvage with intravesical therapy or cystectomy. Like cystectomy, selection enhances outcomes, and we prefer a visually complete TURBT in patients with clinical stage T2, unifocal, nonpalpable disease with no tumor associated hydronephrosis and little to no carcinoma in situ. Realistically, however this probably only constitutes about 15% of patients with muscle-invasive disease (Smith ZL, et al. BJU Int. 2013;doi:10.1111/j.1464-410X.2012.11762.x).
Although, I am cognizant that patients do worse with advancing stage even when pursuing neoadjuvant chemotherapy followed by cystectomy, this series did report a 30% OS in clinical T3/T4 patients without associated hydronephrosis. Interestingly, although we always demand a maximal TURBT, the 50% complete response rate (albeit with limitations) in those patients without maximal TURBT does speak to the efficacy of this approach. Importantly, I was reminded of the very low number of patients who ultimately require cystectomy for toxicity. Whatever your bias, we believe it to be paramount to discuss this option with our patients while engaging the urologist, medical oncologist, radiation oncologist and pathologist in a multidisciplinary fashion. As a surgeon, I continue to remind myself that not everyone referred to me for a cystectomy desires to have one, and that chemotherapy and radiation is not just for those perceived to be to infirm for surgery.

Stephen B. Riggs, MD
Levine Cancer Institute
Carolinas HealthCare System

Disclosure: Riggs reports no relevant financial disclosures.